Researchers have tried to develop ways of protecting the mammalian brain against damage caused by certain types of convulsant drugs which fall within the class of "cholinergic neurotoxins" (discussed below). Two convulsant drugs of particular interest are (1) pilocarpine, which is of interest to researchers studying the causes and mechanisms of epilepsy (Clifford et al 1987; complete citations are provided below) and (2) a compound referred to as soman, a nerve gas that poses a threat in chemical warfare (McLeod et al 1984). Both of those substances can cause continuous seizure activity which persists for hours and causes disseminated brain damage, which typically is fatal unless adequately treated.
In trying to develop effective ways to protect mammalian brains against cholinergic neurotoxins, a substantial amount of effort has focused on tranquilizers and sedatives. Diazepam (sold under the trade name Valium) and phenobarbitol provide partial protection, but only at relatively high doses which are overly sedating, and such protection is unreliable unless the protective agent is administered prior to the convulsant (Clifford et al 1982; Fuller et al 1981). Obviously, pretreatment of front-line troops with heavily sedating doses of Valium would be infeasible for military reasons. Atropine provides some degree of protection against seizures induced by pilocarpine, but only if the atropine is administered prior to the pilocarpine (Honchar et al 1983). Since the nerve gas soman is a cholinesterase inhibitor, various efforts have been made to control its effects using cholinesterase reactivators (Goodman et al 1975). Such efforts provide unreliable results at best, and usually require pretreatment.
At least one published report states that a substance referred to as MK-801 (a glutamate antagonist, discussed below) provides some degree of protection against soman, if administered before soman exposure and if used in conjunction with other protective agents (Braitman et al 1988). However, as mentioned above, pretreatment to protect soldiers against nerve gas is rarely feasible. Perhaps even more importantly, recent research by the inventor of the subject application has discovered that when MK-801, phencyclidine, or ketamine were used in an effort to protect lab animals against pilocarpine, another major class of cholinergic neurotoxin, the seizure activity was made worse and the outcome was rapidly lethal. Although the reasons for those apparently conflicting results are not entirely clear, both sets of results suggest that interactions between the cholinergic and glutamate receptor systems may be relevant to efforts to provide an effective method for protecting the brain against cholinergic neurotoxins. The following sections provide background information on the cholinergic and glutamate receptor systems, and on various types of drugs which have been used to evaluate and control them.